Avila AM, Bebenek I, Mendrick DL, Peretz J, Yao J, Brown PC. Gaps and challenges in nonclinical assessments of pharmaceuticals: An FDA/CDER perspective on considerations for development of new approach methodologies. Regul Toxicol Pharmacol. 2023;139:105345. https://doi.org/10.1016/j.yrtph.2023.105345.

Article  CAS  PubMed  Google Scholar 

Avila AM, Bebenek I, Bonzo JA, Bourcier T, Davis Bruno KL, Carlson DB, et al. An FDA/CDER perspective on nonclinical testing strategies: classical toxicology approaches and new approach methodologies (NAMs). Regul Toxicol Pharmacol. 2020;114:104662. https://doi.org/10.1016/j.yrtph.2020.104662.

Article  CAS  PubMed  Google Scholar 

Jia Y, Jackye P, Bebenek I, Avila A, Alapatt T, Lee B, et al. FDA/CDER/OND experience with new approach mthodologies (NAMs). Int J Toxicol. 2025;10915818251384270. https://doi.org/10.1177/10915818251384270.

Article  Google Scholar 

Portela JMD, Paul P, Moriarty O, Theunissen P, Beken S, Brendler-Schwaab S, et al. Review on organs-on-chips for medicines safety assessment: a European regulatory perspective. ALTEX. 2026;43:98–112. https://doi.org/10.14573/altex.2502061. Accessed 24 May 2026.

U.S. FDA. Roadmap to reducing animal testing in preclinical safety studies [Internet]. 2025. https://www.fda.gov/files/newsroom/published/roadmap_to_reducing_animal_testing_in_preclinical_safety_studies.pdf. Accessed 25 May 2026.

Krebs CE, Camp C, Constantino H, Courtot L, Kavanagh O, McCarthy J, et al. Author guide for addressing animal methods bias in publishing. Adv Sci. 2023;10:2303226. https://doi.org/10.1002/advs.202303226.

Article  Google Scholar 

PCRM. The physicians committee recommends the NIH fund human-based research infrastructure [Internet]. 2025. https://www.pcrm.org/news/good-science-digest/physicians-committee-recommends-nih-fund-human-based-research. Accessed 24 May 2026.

Berggren E, Worth AP. Managing change while phasing out animal testing in chemical safety assessments – a collection of stakeholder experiences and expectations. NAM J. 2026;2:100079. https://doi.org/10.1016/j.namjnl.2026.100079.

Article  Google Scholar 

Hope L, Bailey J. Breaking down the barriers to animal-free research. Altern Lab Anim. 2025;53:215–31. https://doi.org/10.1177/02611929251349465.

Article  PubMed  Google Scholar 

Oyetade OB, Allen DG, Carder J, Farley-Dawson EA, Reinke EN, Marko S, et al. Ways to broaden the awareness, consideration and adoption of new approach methodologies (NAMs)*. ALTEX. ALTEX Edition; 2025;42:714–26. https://doi.org/10.14573/altex.2505281.

U.S. FDA. Implementing alternative methods: agency-wide efforts for advancing development, qualification, and implementation of new alternative methods for product testing [Internet]. 2025 [cited 2026 Jan 26]. https://www.fda.gov/science-research/advancing-alternative-methods-fda/implementing-alternative-methods. Accessed 26 Jan 2026.

Alves VM, Borba J, Capuzzi SJ, Muratov E, Andrade CH, Rusyn I, et al. Oy Vey! A comment on “Machine learning of toxicological big data enables read-across structure activity relationships outperforming animal test reproducibility”. Toxicol Sci [Internet]. 2019;167:3–4. https://doi.org/10.1093/toxsci/kfy286.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Beilmann M, Adkins K, Boonen HCM, Hewitt P, Hu W, Mader R, et al. Application of new approach methodologies for nonclinical safety assessment of drug candidates. Nat Rev Drug Discov. 2025;24:705–25. https://doi.org/10.1038/s41573-025-01182-9.

Article  CAS  PubMed  Google Scholar 

Dao T, Sadrieh N. A CDER perspective: landscape of New approach methodologies (NAMs) submitted in drug development programs. Regul Toxicol Pharmacol. 2026;165:106007. https://doi.org/10.1016/j.yrtph.2025.106007.

Article  PubMed  Google Scholar 

Yao J, Peretz J, Bebenek I, Avila A, Alapatt T, Lee B, et al. FDA/CDER/OND experience with New approach methodologies (NAMs). Int J Toxicol. 2026;45:136–56. https://doi.org/10.1177/10915818251384270.

Article  PubMed  Google Scholar 

U.S. Food & Drug Administration. CDER/Office of new drugs streamlined nonclinical studies and acceptable New approach methodologies (NAMs) [Internet]. [cited 2026 Apr 25]. https://www.fda.gov/about-fda/center-drug-evaluation-and-research-cder/cderoffice-new-drugs-streamlined-nonclinical-studies-and-acceptable-new-approach-methodologies-nams. Accessed 25 Apr 2026.

U.S. Food & Drug Administration. General considerations for the use of new approach methodologies in drug development [Internet]. [cited 2026 Apr 25]. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/general-considerations-use-new-approach-methodologies-drug-development. Accessed 25 Apr 2026.

The 3Rs Collaborative. Microphysiological systems technology hub [Internet]. https://3rc.org/microphysiological-systems-companies/. Accessed 24 May 2026.

Marx U, Beken S, Chen Z, Dehne EM, Doherty A, Ewart L, et al. Biology-inspired dynamic microphysiological system approaches to revolutionize basic research, healthcare and animal welfare. ALTEX. ALTEX Edition. 2025. p. 204–23. https://doi.org/10.14573/altex.2410112.

Marx U, Akabane T, Andersson TB, Baker E, Beilmann M, Beken S, et al. Biology-inspired microphysiological systems to advance patient benefit and animal welfare in drug development. ALTEX. ALTEX Edition. 2020;37:365–94. https://doi.org/10.14573/altex.2001241.

Baker TK, Van Vleet TR, Mahalingaiah PK, Grandhi TSP, Evers R, Ekert J, et al. The current status and use of microphysiological systems by the pharmaceutical industry: the international consortium for innovation and quality microphysiological systems affiliate survey and commentary. Drug Metab Dispos. 2024;52:198–209. https://doi.org/10.1124/dmd.123.001510.

Article  CAS  PubMed  Google Scholar 

Baran SW, Brown PC, Baudy AR, Fitzpatrick SC, Frantz C, Fullerton A, et al. Perspectives on the evaluation and adoption of complex in vitro models in drug development: workshop with the FDA and the pharmaceutical industry (IQ MPS Affiliate). ALTEX. 2022;39:297–314. https://doi.org/10.14573/altex.2112203.

Article  PubMed  Google Scholar 

Tasnim F, Huang X, Lee CZW, Ginhoux F, Yu H. Recent advances in models of immune-mediated drug-induced liver injury. Front Toxicol [Internet]. 2021;3–2021. https://www.frontiersin.org/journals/toxicology/articles/10.3389/ftox.2021.605392. Accessed 24 May 2026.

Lim AY, Kato Y, Sakolish C, Valdiviezo A, Han G, Bajaj P, et al. Reproducibility and robustness of a liver microphysiological system PhysioMimix LC12 under varying culture conditions and cell type combinations. Bioengineering. 2023. https://doi.org/10.3390/bioengineering10101195.

Article  PubMed  PubMed Central  Google Scholar 

Kato Y, Lim AY, Sakolish C, Valdiviezo A, Moyer HL, Hewitt P, et al. Analysis of reproducibility and robustness of OrganoPlate® 2-lane 96, a liver microphysiological system for studies of pharmacokinetics and toxicological assessment of drugs. Toxicol In Vitro. 2022;85:105464. https://doi.org/10.1016/j.tiv.2022.105464.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ewart L, Apostolou A, Briggs SA, Carman CV, Chaff JT, Heng AR, et al. Performance assessment and economic analysis of a human Liver-Chip for predictive toxicology. Commun Med. 2022;2:154. https://doi.org/10.1038/s43856-022-00209-1.

Article  PubMed  PubMed Central  Google Scholar 

Pamies D, Ekert J, Zurich M-G, Frey O, Werner S, Piergiovanni M, et al. Recommendations on fit-for-purpose criteria to establish quality management for microphysiological systems and for monitoring their reproducibility. Stem Cell Rep. 2024;19:604–17. https://doi.org/10.1016/j.stemcr.2024.03.009.

Article  CAS  Google Scholar 

Rusyn I, Sakolish C, Kato Y, Stephan C, Vergara L, Hewitt P, et al. Microphysiological systems evaluation: experience of TEX-VAL tissue chip testing consortium. Toxicol Sci. 2022;188:143–52. https://doi.org/10.1093/toxsci/kfac061.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sakolish C, Reese CE, Luo Y-S, Valdiviezo A, Schurdak ME, Gough A, et al. Analysis of reproducibility and robustness of a human microfluidic four-cell liver acinus microphysiology system (LAMPS). Toxicology. 2021;448:152651. https://doi.org/10.1016/j.tox.2020.152651.

Article  CAS  PubMed  Google Scholar 

Sakolish C, Luo Y-S, Valdiviezo A, Vernetti LA, Rusyn I, Chiu WA. Prediction of hepatic drug clearance with a human microfluidic four-cell liver acinus microphysiology system. Toxicology. 2021;463:152954. https://doi.org/10.1016/j.tox.2021.152954.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sakolish C, Chen Z, Dalaijamts C, Mitra K, Liu Y, Fulton T, et al. Predicting tubular reabsorption with a human kidney proximal tubule tissue-on-a-chip and physiologically-based modeling. Toxicol In Vitro. 2020;63:104752. https://doi.org/10.1016/j.tiv.2019.104752.

Article  CAS  PubMed  Google Scholar 

Sakolish C, House JS, Chramiec A, Liu Y, Chen Z, Halligan SP, et al. Tissue-engineered bone tumor as a reproducible human in vitro model for studies of anticancer drugs. Toxicol Sci. 2020;173:65–76. https://doi.org/10.1093/toxsci/kfz220.

Article  PubMed  PubMed Central  Google Scholar 

Liu Y, Sakolish C, Chen Z, Phan DTT, Bender RHF, Hughes CCW, et al. Human in vitro vascularized micro-organ and micro-tumor models are reproducible organ-on-a-chip platforms for studies of anticancer drugs. Toxicology. 2020;445:152601. https://doi.org/10.1016/j.tox.2020.152601.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sakolish C, Weber EJ, Kelly EJ, Himmelfarb J, Mouneimne R, Grimm FA, et al. Technology transfer of the microphysiological systems: a case study of the human proximal tubule tissue chip. Sci Rep. 2018;8:14882. https://doi.org/10.1038/s41598-018-33099-2.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sakolish C, Lin H-C, Moyer HL, Ford LC, Christen CH, Wetmore BA, et al. An in vitro-in silico workflow for predicting renal clearance of environmental chemicals and drugs. Toxicology. 2026;519:154336. https://doi.org/10.1016/j.tox.2025.154336.

Article  CAS  PubMed